Caspases inhibitors enhance regeneration of neonatal spinal motoneurons after root avulsion

Abstract

We have previously demonstrated that the administration of caspase inhibitors benzyloxycarbonyl-Asp(OMe)fluoromethylketone (Boc-D-FMK) protected the avulsed spinal motoneurons from death for more than 8 weeks while the neuroprotective effect of N-acetyl-Asp-Glu-Val-Asp aldehyde (Ac-DEVD-CHO) was only lasted for 14 days. The present study examined whether in neonatal animals, inhibition of caspases could enhance the regeneration and reinnervation of injured motoneuron. Boc-D-FMK and Ac-DEVD-CHO promoted 62% and 44% motoneuron regeneration respectively when the peripheral nerve (PN) graft was implanted immediately after the lesion. When the PN graft was implanted 2 weeks following the injury, 53% of motoneurons could regenerate their axons into the PN graft after treatment with Boc-D-FMK. In addition, 39% of the motoneuron axons were able to reinnervate the denervated biceps muscle. Some morphologically normal neuromuscular junctions were reformed through a PN bridge joining the avulsed spinal motoneurons to the biceps. Our results indicated that general caspase inhibitor is essential for the regeneration and reinnervation of the axotomized motoneurons after root avulsion in neonates. Supported by The Hong Kong Research Grants Council